Forskokin, a diterpene, activates adenylate cyclase in a variety of tissues and cells. Activation by forskolin is synergistic with receptor-mediated activation by biogenic amines, peptides, prostaglandins and adenosine and stabilized the enzyme against receptor-mediated inhibition by norepinephrine and against inhibition mediated through the adenosine P-site. In certain cells forskolin-activation of adenylate cyclase is minimal unless the inhibitory guanyl nucleotide (Ni) subunit of the enzyme is inactivated by N-ethylmaleimide. Forskolin prevents platelet aggregation, potentiates bradykinin-induced and inhibits prostaglandin-induced plasma exudation via activation of adenylate cyclase. At least three classes of adenosine receptors occur in brain, a ubiquitous low affinity A2-receptor stimulatory to adenylate cyclase which synergizes in cerebrum with alpha-adrenergic and H1-histaminergic input, a high affinity A2-receptor stimulatory to striatal cyclase and ubiquitous A1-receptor inhibitory to cyclase. The A2-receptors have much less bulk tolerance at N6-position of agonists and at N1- and N7-position of xanthine antagonists, than does the A1-receptor, which has allowed definition of selective A1-agonists and antagonists. An 8-phenyl substituent enhances the potency of xanthine antagonists at both A1- and A2-receptors, but certain phenyl substituents do confer selectivity.